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Int. J. Mol. Sci. 2015, 16(1), 1907-1927; doi:10.3390/ijms16011907

Melatonin Stimulates Dendrite Formation and Complexity in the Hilar Zone of the Rat Hippocampus: Participation of the Ca++/Calmodulin Complex

Laboratorio de Neurofarmacología, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México-Xochimilco No. 101, Col. San Lorenzo-Huipulco, CP 14370 Tlalpan, DF, Mexico
Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Av. Ciudad Universitaria 3000, CP 04360 Coyoacán, DF, Mexico
Author to whom correspondence should be addressed.
Academic Editor: Rudiger Hardeland
Received: 31 July 2014 / Accepted: 7 January 2015 / Published: 16 January 2015
(This article belongs to the Special Issue Advances in the Research of Melatonin 2014)
View Full-Text   |   Download PDF [6414 KB, uploaded 16 January 2015]   |  


Melatonin (MEL), the main product synthesized by the pineal gland, stimulates early and late stages of neurodevelopment in the adult brain. MEL increases dendrite length, thickness and complexity in the hilar and mossy neurons of hippocampus. Dendrite formation involves activation of Ca2+/Calmodulin (CaM)-dependent kinase II (CaMKII) by CaM. Previous work showed that MEL increased the synthesis and translocation of CaM, suggesting that MEL activates CaM-dependent enzymes by this pathway. In this work we investigated whether MEL stimulates dendrite formation by CaMKII activation in organotypic cultures from adult rat hippocampus. We found that the CaMKII inhibitor, KN-62, abolished the MEL stimulatory effects on dendritogenesis and that MEL increased the relative amount of CaM in the soluble fraction of hippocampal slices. Also, PKC inhibition abolished dendritogenesis, while luzindole, an antagonist of MEL receptors (MT1/2), partially blocked the effects of MEL. Moreover, autophosphorylation of CaMKII and PKC was increased in presence of MEL, as well as phosphorylation of ERK1/2. Our results indicate that MEL stimulates dendrite formation through CaMKII and the translocation of CaM to the soluble fraction. Dendritogenesis elicited by MEL also required PKC activation, and signaling through MT1/2 receptors was partially involved. Data strongly suggest that MEL could repair the loss of hippocampal dendrites that occur in neuropsychiatric disorders by increasing CaM levels and activation of CaMKII. View Full-Text
Keywords: melatonin; dendrites; calmodulin-kinase II; calmodulin; hippocampus; neuropsychiatric disorders melatonin; dendrites; calmodulin-kinase II; calmodulin; hippocampus; neuropsychiatric disorders

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MDPI and ACS Style

Domínguez-Alonso, A.; Valdés-Tovar, M.; Solís-Chagoyán, H.; Benítez-King, G. Melatonin Stimulates Dendrite Formation and Complexity in the Hilar Zone of the Rat Hippocampus: Participation of the Ca++/Calmodulin Complex. Int. J. Mol. Sci. 2015, 16, 1907-1927.

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